Recently, indirect calorimetry has frequently been used together with hyperinsulinemic clamps. With few exceptions, however, no attention was paid in these studies to the possible effects of hyperinsulinemia on urea nitrogen (N) pool size and the consequences of such changes on the calculated rates of protein, lipid, and carbohydrate (CHO) oxidation. We have determined the effects of euglycemic-hyperinsulinemic clamps on urea N pool size, urinary N excretion, and rates of protein, lipid, and CHO oxidation (measured by indirect calorimetry) in six normal men. Insulin infusion (1 mU.kg-1.min-1) increased peripheral venous insulin concentration from 7 +/- 1.2 (mean +/- SE) to 51 +/- 4 microU/ml. Glucose concentration was clamped at 84 +/- 1.1 mg/dl. Between 0 (preclamp) and 360 min (end of clamp), blood urea N concentration decreased from 17.2 +/- 1.1 to 11 +/- 0.8 mg/dl (P less than .001), and the urea N pool decreased from 604 +/- 41 to 388 +/- 30 mmol (P less than .001). The urea N production rate decreased from 461 +/- 91 (preclamp) to 91 +/- 63 mumol/min during the last 4 h of the clamp (P less than .05). Urinary N excretion remained unchanged (705 +/- 113 vs. 905 +/- 125 mumol/min, NS). Correction of urinary N excretion for insulin-induced reductions in the urea N pool resulted in the following changes in substrate oxidation rates (calculated for the last 4 h of the clamp).(ABSTRACT TRUNCATED AT 250 WORDS)